Time-dependent alteration of insulin-like growth factor gene expression during nerve regeneration in regions of muscle enriched with neuromuscular junctions

Insulin-like growth factors (IGFs) increase the rate of motor axon elongati on, prevent motoneuron death, and may support the reestablishment of synaps es following nerve injury. In situ hybridization was used in the present st udy to examine the temporal and spatial distribution of IGF gene expression in soleus muscle following sciatic nerve crush in rats. In intact muscle, IGF-II gene expression was generally low, and localized to interstitial cel ls, possibly fibroblast and Schwann cells. These cells were found in the mi ddle of muscle which is enriched in neuromuscular junctions. IGF-II gene ex pression, 4-6 days postcrush, was increased in interstitial cells. Thereaft er, IGF-II gene expression was also increased in muscle cells or cells clos ely associated with muscle fibers, such as satellite cells. IGF-II gene exp ression was increased to a much greater extent in the midregion of muscle e nriched in end-plates than in the two ends of muscle, but returned towards normal following the reestablishment of functional synapses. On the other h and, IGF-I gene expression was only slightly increased following nerve crus h, and this increase was associated with interstitial, but not muscle cells . These results show that the IGF-I and IGF-II genes are regulated by indep endent signals and may play separate roles during nerve regeneration. For e xample, a regional increase in IGF-II gene expression may support preferent ial nerve terminal sprouting in the middle of muscle enriched in neuromuscu lar junctions, thereby increasing the probability for the reestablishment o f synapses. (C) 1999 Elsevier Science B.V. All rights reserved.